We suspected some spontaneous hybridization between tumor cells and host cells in the Ehrlich ascites tumor (EAT) maintained for many years in CF1 mice from the chromosome constitution of certain tumor cells. This was confirmed by the acquisition of host specific T6 chromosome markers by tumor cells after a transfer of EAT in CBA/HT6 mice. The incidence of T6 marker positive tumor cells increased with increasing number of passages within CBA/HT6 mice, but they lost some chromosomes as evidenced by a return to the original modal chromosome number. Chromosome elimination was identified morphologically at mitosis which appeared as micronuclei in interphase cells. The nature of chromosomes lost are under study. Host components in tumor-host cell heterokaryons were identified as lymphocytes, monocytes and macrophages. Since host-host cell heterokaryons were also found, the fusion appeared nonspecific. Prolonged intraperitoneal passage of EAT in a different host strain also produced alterations in subcutaneous tumorigenicity: it led to acquisition of tumorigenicity for the propagating host and loss of tumorigenicity for the original host strain, consistent with antigenic changes that are explicable by hybridization and chromosome loss. Studies are in progress: 1) to select hybrid populations in vivo and in vitro, 2) to evaluate whether there is an immunoselection of hybrids, and 3) to identify the isoantigenic changes resulting from in vivo hybridization. BIBLIOGRAPHIC REFERENCES: P.K. Lala and L. Kaizer. Kinetics of host mononuclear cells in TA-3(St) solid tumors. Proc. 89th Ann. Meeting Amer. Assoc. Anat. 1976, in press. (Abstract) P.K. Lala and S. Garnis. Characterization of small lymphocytes in the Ehrlich ascites tumor. Proc. 67th Ann. Meeting Amer. Assoc. Cancer Res. 1976, in press. (Abstract)